Changes in the Content of Sphingolipids in the Nigrostriatal Dopaminergic System in the Brain of Mice with a Neurotoxic Model of Parkinson’s Disease

Alessenko, A. V.; Блохин, В. Е.; Shupik, M. A.; Gutner, U. A.; Lebedev, A. T.; Maloshitskaya, O. A.; Sokolov, Sergey; Ugrumov, M. V.

doi:10.1134/s1819712421020021

Cited by 1 publication

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“…The data obtained in this study in the MPTP model of the early clinical stage of PD are in good agreement with the absence of changes in the total concentration of sphingomyelins shown earlier in the MPTP model of the advanced clinical stage of PD [ 27 ]. It seems that the MPTP models we used reproduce well the changes in sphingomyelin metabolism in PD patients.…”

Section: Discussionsupporting

confidence: 88%

“…This led to an increase in the total concentration of hexosylceramides in the striatum in the early clinical-stage model ( Table 2 ). When comparing the data obtained in this study ( Table 2 ) and in our previous research [ 27 ], it can be assumed that an increase in the level of monohexosylceramides can be expected in patients but only at the advanced clinical stage of PD, as seen in the corresponding MPTP models [ 27 ]. As for the role of monohexosylceramides in the pathogenesis of PD, data on this issue are extremely limited in existing published research.…”

Section: Discussionmentioning

confidence: 57%

“…Surprisingly, this change was leveled out at the early clinical stage. However, as shown in our previous research, the concentration of ceramides in the SN doubles in the advanced clinical-stage model, as the level of three types of ceramides rises then: d18:1/16:0, d18:1/18:0, and d18:1/24:1 [ 27 ]. Our data in this and previous studies are consistent with the general idea that intracellular accumulation of ceramides is one of the triggers and modulators of neurodegeneration [ 35 ].…”

Section: Discussionmentioning

confidence: 60%

“…Our recent study [ 27 ] was one of the first to focus on changes in sphingolipid content in the nigrostriatal system, striatum and the SN, in mice with MPTP modeling of the advanced (late) clinical stage of PD (four subcutaneous injections of MPTP at a single dose of 10 mg/kg with an interval of 2 h between injections). In that study, we showed the great potential of this approach for assessing changes in sphingolipid metabolism in the pathogenesis of PD.…”

Section: Discussionmentioning

confidence: 99%

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The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

et al. 2022

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Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 57%